Profiling Chromatin Accessibility at Single-cell Resolution

Overview

Journal Genomics Proteomics Bioinformatics

Specialty Biology

Date 2021 Feb 13

PMID 33581341

Citations 15

Authors

Sarthak Sinha

Ansuman T Satpathy

Weiqiang Zhou

Hongkai Ji

Jo A Stratton

Arzina Jaffer

Nizar Bahlis

Sorana Morrissy

Jeff A Biernaskie

Affiliations

Soon will be listed here.

Abstract

How distinct transcriptional programs are enacted to generate cellular heterogeneity and plasticity, and enable complex fate decisions are important open questions. One key regulator is the cell's epigenome state that drives distinct transcriptional programs by regulating chromatin accessibility. Genome-wide chromatin accessibility measurements can impart insights into regulatory sequences (in)accessible to DNA-binding proteins at a single-cell resolution. This review outlines molecular methods and bioinformatic tools for capturing cell-to-cell chromatin variation using single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) in a scalable fashion. It also covers joint profiling of chromatin with transcriptome/proteome measurements, computational strategies to integrate multi-omic measurements, and predictive bioinformatic tools to infer chromatin accessibility from single-cell transcriptomic datasets. Methodological refinements that increase power for cell discovery through robust chromatin coverage and integrate measurements from multiple modalities will further expand our understanding of gene regulation during homeostasis and disease.

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